When Does Human Life Begin a Scientific Perspective

8/7/2019 When Does Human Life Begin a Scientific Perspective

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WHITE PAPER

Volume 1, Number 1

October 2008A Scientifc PerspectiveWhen Does Human Lie Begin?

Maureen L. Condic

Senior Fellow

Westchester Institute for Ethics & the Human Person

Associate Professor of Neurobiology and Anatomy

at the University of Utah School of Medicine

Foreword by

Richard John Neuhaus

Editor in Chief, First Things

The Westchester InstituteFor Ethics & the Human Person


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Westchester Institute White Paper Series

Volume 1, Number 1

The Westchester Institute or Ethics & the Human Person

P.O. Box 78, 582 Columbus Ave.

Thornwoo, NY 10594

A Scientifc Perspective

Maureen L. Conic

When Does Human Lie Begin?


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Westchester Institute White Paper

When Does Human Life Begin?


Copyright 2008 by Te Westchester Institute or Ethics & the Human Person

Printed in the United States o America

All rights reserved. No part o this publication may be used or reproduced in anymanner without the written permission o the Westchester Institute or Ethics & theHuman Person, except in the case o brie quotations embodied in critical articlesand reviews.

Cover ArtCopyright 2008 by Richard G. Rawlins, Ph.D. - Custom Medical Stock PhotoAll Rights Reserved

Te cover photograph shows a light micrograph o a cryopreserved, unicellular hu-man zygote approaching syngamy. Human embryos, such as this one, are routinelycreated byin vitro ertilization in eorts at assisted reproduction, and are sometimesdesignated or research in which they are deliberately destroyed. Given the currentstate o biotechnology, most photos o human embryos in circulation today are madepossible by these situations which o themselves are unnatural to human embryos.Te Executive Director o the Westchester Institute, while authorizing the use othis photo, wishes to express his own moral objection to the in vitro production ohuman embryos.


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CONTENTSForeword

Introduction & Acknowledgement

Summary

When Does Human Lie Begin? A Scientic Perspective

How Has the Beginning o Lie Been Dened?

What is the Scientic Basis or Distinguishing Dierent ypes o Cells?

How Does the Zygote Dier From Sperm and Egg?

Is the Zygote Merely a New Human Cell or is it a New Human Individual?

Why Isnt Syngamy the Beginning o a New Human Lie?

What are Parthenotes, Hydatidiorm Moles, and Clones?

Does a Human Being Control its Own Development or is it Manuactured?

Author

Glossary

Figure 1

Select Bibliography

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It is really ar past time to clear the air o the smog that obscures and conuses de-bates about abortion, embryonic research, cloning, and related issues.

Among the chie obuscations and conusions is the claim that we do not know whenhuman lie begins. Tis requently takes the orm o claiming that the question isa matter o aith or religious belie. Nothing could be arther rom the truth, as islucidly and convincingly demonstrated in this White Paper.

When a human lie begins is a question o science. Te ethicist Peter Singer o Princ-eton University is amous, or notorious, or his advocacy o selective inanticide orbabies who are born and then ound to be deective in a way that makes them un-wanted. Most people will nd that argument morally abhorrent. But Singer is rightabout one thing. As he has said on many occasions, he and the pope are in completeagreement on when human lie begins.

Te debate in our society and others is not over when human lie begins but is overat what point and or what reasons do we have an obligation to respect and protectthat lie. Beore we can get to that argument, however, we need to clear the smogsurrounding the question o when human lie begins. Tis White Paper makes aninvaluable contribution to that end.

It is sometimes said that the abortion debate is about values rather than acts. Anhonest debate about abortion, however, is about values based on acts. I we dontget the acts right, we will not get our values right. Establishing by clear scientic

evidence the moment at which a human lie begins is not the end o the abortiondebate. On the contrary, that is the point rom which the debate begins.

Troughout history, there have been many societies that have decided that some hu-man lives are more worthy o respect and protection than other human lives. Whilesome such decisions are repugnantly racist, as in the case o Nazi Germany, or ideo-logical, as in the case o Soviet and Maoist communism, others have made the deci-sion on more sophisticated, even apparently humane, grounds. Tat is certainly truein the case o most o those who support an unlimited abortion license in our society.What we should not evade or obscure is the nature o the decision under discussion.

FOREWORd


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Finally, Christians believe that all truth is one because God, who is the source andend o all truth, is one. On the question at hand, as on other questions, there is notension, never mind conict, between science and aith. Faith and science, whenrightly understood, are in the service o truth. Tis White Paper is not an exercise intheology. Nor is it an exercise in ethics or moral reasoning. It is a scientic examina-tion o acts which, when clearly understood, provide the subject matter upon whichother orms o reasonable reectionmedical, moral, legal, political, and theolog-icalcan then be brought to bear. All who are involved in these debates should begrateul to the Westchester Institute or Ethics & the Human Person or providingthis important clarication o what it is that we are debating.

Richard John NeuhausEditor in ChieFirst Tings


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It is my great pleasure to introduce Dr. Maureen Condics When Does Human LieBegin? as the rst White Paper o the Westchester Institute or Ethics & the HumanPerson. Each contribution to this new White Paper series intends to oer a cogentand measured argument on a question o great moment, and Dr. Condics inauguralpaper provides us with nothing less.

Tough human reason is not dependent upon biological ndings or its certaintythat a new human lie wholly begins at some discrete moment, it is nonethelessdependent on the careul investigations o biologists like Dr. Condic to determineprecisely where and when that discrete moment occurs.

In this White Paper, Dr. Condic challenges some o the conventional wisdom aboutthat moment and argues that a coherent and non-arbitrary analysis o the scienticdata orcibly points to the conclusion that a new human lie commences at theprecise moment when the membranes o the sperm and egg cells use. Specically,she critiques the more common position that human lie begins about 24 hours laterduring an event called syngamy (the breakdown o the two pronuclear membranes inthe new cell, which results rom the usion o sperm and egg).

In this way, Dr. Condic accomplishes in the eld o developmental biology exactlywhat the Westchester Institute hopes to oster in the realm o ethical reection:namely, rigorous advancement o the discussion regarding unsettled questions oparamount moral concern.

With Dr. Condics contribution, we are proud and delighted to launch our WhitePaper series.

Fr. Tomas Berg, L.C., Ph.D.Executive DirectorTe Westchester Institute or Ethics & the Human Person

Te Westchester Institute is prooundly grateul to Antoine Puech, whose generosityhas made this publication possible.

INTROdUCTION

ACkNOWLEdgEMENT


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Resolving the question o when human lie begins is critical or advancing a rea-soned public policy debate over abortion and human embryo research. Tis articleconsiders the current scientifc evidence in human embryology and addresses twocentral questions concerning the beginning o lie: 1) in the course o sperm-egginteraction, when is a new cell ormed that is distinct rom either sperm or egg?and 2) is this new cell a new human organismi.e., a new human being? Basedon universally accepted scientifc criteria, a new cell, the human zygote, comes intoexistence at the moment o sperm-egg usion, an event that occurs in less than asecond. Upon ormation, the zygote immediately initiates a complex sequence oevents that establish the molecular conditions required or continued embryonicdevelopment. Te behavior o the zygote is radically unlike that o either spermor egg separately and is characteristic o a human organism. Tus, the scientifcevidence supports the conclusion that a zygote is a human organism and that thelie o a new human being commences at a scientifcally well defned moment oconception. Tis conclusion is objective, consistent with the actual evidence, andindependent o any specifc ethical, moral, political, or religious view o human lieor o human embryos.

SUMMARY


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1

Te question o when human lie begins is one o considerable ethical, legal, and po-litical importance, particularly or public policy debates over abortion and embryonicstem cell research. Recently, a number o our nations most prominent political lead-ers have weighed in on this question, proposing two very dierent sorts o answers.On the one hand, Nancy Pelosi, the Speaker o the House o Representatives, stated,I dont think anybody can tell you when human lie begins. 1 Her sentiment hasbeen echoed by Senator Biden,2 who said that he believes lie begins at conception,but that this is merely a religious opinion that could not legitimately be the basis orpublic policy. In contrast, Senator McCain has condently stated that lie begins atthe moment o conception,3 although he did not oer a precise denition o whenthis moment occurs.

1 Nancy Pelosi, Meet the Pressinterview with Tom

Brokaw, August 24, 2008. Transcript available at http://

www.msnbc.msn.com/id/26377338/page/3/ (accessed

9/12/2008; transcript on le with author).

2 Joseph Biden, Meet the Pressinterview with Tom

Brokaw, September 7, 2008. Transcript available at http

www.msnbc.msn.com/id/26590488/page/4/ (accessed

9/12/2008; transcript on le with author).

3 John McCain, Saddleback Presidential Forumintervie

with Rick Warren, August 16, 2008. Transcript available

http://transcripts.cnn.com/TRANSCRIPTS/0808/17/se.0

html (accessed 9/12/08; transcript on le with author).

HOW HAS THE BEgINNINg

OF LIFE BEEN dEFINEd?

When in the course o prenatal development a new human being comes into existenceis not an easy question to answer; indeed, it has been answered in many ways through-out history, based on the understanding o human development available at any giventime. Advances in the study o human embryology have sharpened our ocus to anincreasingly narrow developmental time-rame. Modern science indicates that the

beginning o lie occurs sometime ater the ertilization o an ovum by a sperm cell, yetertilization itsel is surprisingly difcult to dene. Te events immediately ollowingthe usion o sperm and eggand prior to the rst cell division (an approximately 24-hour period also reerred to as the rst cell cycle)have typically been viewed as parto the process o ertilization (see Figure 1, p. 17). At some point during this period,an embryo orms, but precisely when this occurs has been the subject o considerabledisagreement and debate.

Te point at which ertilization ends and embryonic development commences iscommonly placed at syngamy, the time when the membranes surrounding thenuclei derived rom the sperm and the egg break down in preparation or the rst celldivision (see Figure 1E, p. 17). Indeed, many textbooks devoted to the topic o humanembryology,4 as well as the legal codes o a number o countries 5 and states withinthe USA,6 dene the completion o ertilization and beginning o lie in this man-ner. Yet this is not the only point at which lie is said to begin. Recently,7 it has beenasserted that the lie and moral status o the embryo begin at the eight-cell stage,because zygotic transcription (the active utilization o embryonic genes) commencesat this time; and prior to this moment, whatever is happening in the ertilized egg 8is being driven by maternal actors.9 Some push the onset o lie to even later, to theormation o specic structures or the onset o specic developmental processes.10

Modern science indicates that the beginning o lieoccurs sometime ater the ertilization o an ovumby a sperm cell, yet ertilization itsel is surprisinglydicult to defne.

4 For example: Fertilization is a complex sequence o

coordinated events that begins with contact between a

sperm and an oocyteand ends with the intermingling

o maternal and paternal chromosomes at metaphase

o the rst mitotic division o the zygote [Keith L. Moor

and T.V.N. Persaud, The Developing Human, 7th ed.

(Philadelphia: Saunders-Elsevier, 2003), 31]; At this po

[syngamy] the process o ertilization can be said to be

complete and the ertilized egg is called a zygote [Bruc

M. Carlson, Human Embryology and Developmental Bio

ogy, 3rd ed. (Philadelphia: Mosby-Elsevier, 2004), 36].

5 International Consortium o Stem Cell Networks, Glo

Regulation o Human Embryonic Stem Cell Research a

Oocyte Donation http://www.stemcellcentre.edu.au/P

Global_Regulation_HESC_Research_Oocyte_Donation.

(accessed October 6, 2008).

6 For example: VA. CODE ANN. S 20-156 (2004): Emb

means the organism resulting rom the union o a sperm

and an ovum rom rst cell division until approximately

end o the second month o gestation.

7 Philip G. Peters, Jr., The Ambiguous Meaning o Hum

Conception, University of California-Davis Law Review

40 (2006):199-228.


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Te act that lie is truly a continuum urther complicates the question o whena new lie commences. Most human beings are produced rom the union o twopreexisting cells: sperm and egg. Sperm and egg cells were, in turn, generated romliving cells that preceded them in the testes and ovaries, and so orth, back inde-nitely to the beginning o all lie. In light o the continuous nature o living cells,dening the beginning o a new organism as the onset o zygotic transcription orthe breakdown o nuclear membranes is intellectually and scientically unsatisying.Tese are arbitrary points along a continuum o liepoints that are likely to varyconsiderably across closely related species and across individuals o the same species.Such denitions are logically akin to linking the beginning o personhood to theeruption o teeth in an inant or to the onset o menses in an adolescentthey arearbitrary, variable, and not indicative o any undamental change in the entity underconsideration.

Te continuum o cellular liewith living cells giving rise to new types o cells and,ultimately, to new individualshas led some to conclude that the question o whenlie begins is unanswerable. Because cellular lie exists in a continuum, this line oreasoning concludes, there can be no meaningul point at which a new human lieis said to begin. Yet i this view is correct, we are let with a serious ethical dilemma:while no one objects to the destruction o ordinary human cells or biomedical re-search, the use ohuman beingsor such purposes is universally condemned. Clearly,some non-arbitrary criteria must be established to determine when living humancells give rise to a new individual human being.

8 Reerring to the product o sperm-egg usion as a

ertilized egg is misleading; once an egg is ertilized, it

ceases to be an egg. This term avoids the central question

o what kind o cell is produced by ertilization.

9 There is good evidence rom mouse and rom human

embryos that the zygotic genome becomes active beore

the rst cell division: Luke Martin-McCarey et al.,

RGS14 is a Mitotic Spindle Protein Essential rom the

First Division o the Mammalian Zygote, Developmental

Cell7, no. 5 (November 2004): 763-9; Asangla Ao et al.,

Transcription o Paternal Y-linked Genes in the Human

Zygote as Early as the Pronucleate Stage, Zygote2,

no. 4 (November 1994): 281-7; Robert Daniels et al.,

XIST Expression in Human Oocytes and Preimplantation

Embryos American Journal of Human Genetics61, no.

1 (July 1997): 33-9; Richard M. Schultz, Regulation o

Zygotic Gene Activation in the Mouse, Bioessays15, no.8 (August 1993): 531-8; Christine Bouniol, Eric Nguyen,

and Pascale Debey, Endogenous Transcription Occurs at

the 1-cell Stage in the Mouse Embryo, Experimental Cell

Research218, no. 2 (May 1995): 57-62; Anthony T. Dob-

son et al., The Unique Transcriptome Through Day 3 o

Human Preimplantation Development, Human Molecular

Genetics13, no. 14 (July 2004):1461-70.

10 It is commonly claimed that lie begins with the

ormation o the inner cell mass o the embryo (~our

days post ertilization), or when the embryo implants in

the uterus (~5-6 days post ertilization), or at the onset o

gastrulation (~two weeks ater ertilization).

WHAT IS THE SCIENTIFIC BASIS FOR dISTINgUISHINg

dIFFERENT TYPES OF CELLS?

Science relies on detailed observation to determine when a change in cell type hasoccurred. Troughout embryogenesis, cells continuously change rom one type toanother, and these transitions can be reliably detected. Scientic distinctions aremade between various cell types, based on two relatively simple criteria: cells areknown to be dierent rom each other because they have dierent composition (i.e.,dierent genes are expressed, dierent proteins produced, etc.) and because theyexhibit distinct types o cell behavior. For example, a transient embryonic populationo cells, known as neural crest cells, produces a variety o dierent cell types duringdevelopment, including the progenitors o all the sensory neurons o the body. Asneural crest cells convert into this new cell type (sensory neural progenitors), they

undergo a number o observable changes: they stop migrating, begin a period omore active cell prolieration, begin to express dierent genes, and assume a dierentcellular morphology. Tese changes are the basis or asserting that neural crest cellsand sensory neural progenitors are distinctcell types.


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When cells are classied into specic types, dierences in either composition orbehavior are the bases or all scientifc, as opposed to arbitrary, distinctions. I, orexample, scientists were to propose that during embryonic development a novel celltype exists between a neural crest and a sensory neural progenitor cell, they wouldhave to provethis assertion by pointing to specic material or behavioral characteris-tics that distinguish this cell both rom the cell that gave rise to it and rom the cell itsubsequently generatesor risk having their assertions dismissed as mere antasy.

In considering the question o when the lie o a new human being commences, wemust rst address the more undamental question o when a new cell, distinct romsperm and egg, comes into existence: when during the interactions o sperm and eggdo we observe the ormation o a new cell with both a material composition and adevelopmental pathway (i.e., a pattern o cell behavior) that are distinct rom thecells giving rise to it? Tese two criteria (unique composition and behavior) are usedthroughout the scientic enterprise to distinguish one cell type rom anotherandi we reject them as the basis or making such distinctions, the only alternative is tomake an essentially arbitrary decision.

HOW dOES THE zYgOTE dIFFER

FROM SPERM ANd Egg?

Te basic events o early development are both reasonably well characterized and en-tirely uncontested. Following the binding o sperm and egg to each other, the mem-branes o these two cells use, creating in this instant a single hybrid cell: the zygote

or one-cell embryo (see Figure 1A). Cell usion is a well studied and very rapid event,occurring in less than a second.11 Because the zygote arises rom the usion o twodierent cells, it contains all the components o both sperm and egg, and thereorethe zygote has a unique molecular composition that is distinct rom either gamete.

Subsequent to sperm-egg usion, events rapidly occur in the zygote that do not nor-mally occur in either sperm or egg. Te contents o what was previously the sperm,including its nucleus, enter the cytoplasm o the newly ormed zygote. Within min-utes o membrane usion, the zygote initiates changes in its ionic composition12 thatwill, over the next 30 minutes, result in chemical modications o the zona pellucida,an acellular structure surrounding the zygote (Figure 1B). Tese modications blocksperm binding to the cell surace and prevent urther intrusion o additional sperma-tozoa on the unolding process o development. Tus, the zygote acts immediately

and specically to antagonize the unction o the gametes rom which it is derived;while the goal o both sperm and egg is to nd each other and to use, the rst acto the zygote is immediately to prevent any urther binding o sperm to the cell sur-ace. Clearly, then, the prior trajectories o sperm and egg have been abandoned, anda new developmental trajectorythat o the zygotehas taken their place.

11 Ulyana Vjugina and Janice P. Evans, New Insights

the Molecular Basis o Mammalian Sperm-Egg Membr

Interactions, Frontiers in Bioscience13, no. 2 (Januar

2008): 462-76; Meital Oren-Suissa and Benjamin Podb

wicz, Cell Fusion During Development, Trends in CellBiology17, no. 11 (November 2007): 537-46.

12 Llewellyn J. Cox et al., Sperm Phospholipase Czet

rom Humans and Cynomolgus Monkeys Triggers Ca2+

Oscillations, Activation and Development o Mouse

Oocytes, Reproduction124, no. 5 (November 2002): 6

23; Christopher M. Saunders, Karl Swann, and F. Antho

Lai, PLCzeta: A Sperm-Specic PLC and its Potential

Role in Fertilization, Biochemical Society Symposia74

(2007): 23-36.

Fig 1A Sperm-Egg Fusion

!Zona

Pellucida

Ovum

Sperm

Maternalnucleus

!

Paternal

nucleus

Zygote

!Polar

body

Paternal

nucleus

!

Fig 1B Zygote Formation

Fig 1C Early Acts of the Zygote

Fig 1D Onset of Zygotic Transcription


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Within the rst 30 minutes ollowing sperm-egg usion, the maternally derived nu-cleus completes its nal round o meiotic division (Figure 1C), a process initiated byactors contributed by the sperm.13 Tus, or a brie time, the zygote is a triploid cell,containing one set o DNA rom the sperm and two sets o DNA rom the oocyte.Te completion o meiosis in the maternally derived nucleus converts this triploid cellto a diploid state and establishes the denitive (i.e., nal) genome o the zygote.14 Byeliminating hal o the maternally contributed DNA, the zygote acts in the interest oits own subsequent development to establish a genetic state that is dissimilar to that ogametes and uniquely capable o supporting continued embryonic development.

Following completion o meiosis, the maternally and paternally derived nuclei under-go rapid structural and chemical changes. Beginning within 30 minutes, protamineassociated with the paternally derived DNA is replaced by histone,15 generating apaternal nucleus that is actually a hybrid o paternally derived DNA and mater-nally derived protein (Figure 1C). Substitution o histone or protamine is requiredor DNA replication and zygotic transcription, processes that will not commence orseveral hours. Tus, modication o the paternal nucleus anticipates the subsequentsteps o zygotic development and can be understood only as part o an ongoingdevelopment that is unique to the zygote and distinct rom that o sperm and egg.Moreover, the observation that maternally derived proteins bind to and alter theunction o both egg- and sperm-derived DNA indicates that molecular interactionsbetween the maternally and paternally derived components o the zygotic genomecommence almost immediately ater sperm-egg usion.

Within the rst hour ollowing sperm-egg usion, the DNA o both pronuclei isdemethylated, but the paternally derived nucleus is more rapidly and extensivelymodied16 (Figure 1C). Demethylation is required or normal patterns o geneexpression to occur when zygotic transcription begins approximately ten hours later,and it is, thereore, also part o a developmental sequence that is initiated by sperm-egg usion and unique to the zygote.

Within 8-10 hours ollowing sperm-egg usion, both the maternally and paternallyderived nuclei replicate their DNA in anticipation o the rst round o cell division,which will not occur or another 15 hours17 (Figure 1D). Te timing o the onset oDNA replication depends on actors rom the sperm,18 again indicating that mater-nally and paternally derived components o the zygote are interacting to generate acoordinated pattern o development well beore the end o the rst cell cycle.

Immediately ollowing the period o DNA replication, transcription begins in bothhalves o the genome19 (Figure 1D). Development beyond the two-cell stage criti-cally depends on expression o zygotic genes,20 indicating that even at the one-cellstage, the zygote is directing its own development. Interestingly, at this early stage,expression o maternally derived genes is actively blocked by the male pronucleus;transcription o the paternally derived DNA is our- to ve-old greater than that o

13 See ootnote 12.

14 The objection is commonly raised that or the rst 30

minutes ollowing sperm-egg usion, the zygote is not

genetically unique and thereore cannot be a new hu-

man individual. However, the transiently triploid genome

o the zygote is entirely unique and distinct rom that o

either parent. Moreover, even the denitive genome

present ater 30 minutes continues to be altered in many

ways during development (X-inactivation in emales, elim-

ination o DNA in b-lymphocyte maturation, epigenetic

changes, etc.), without compromising the unique identity

o the individual. The DNA eliminated at meiosis is not

irrelevant to the subsequent development o the zygote.

The unique pattern o development a zygote undergoes

is not determined solely by the DNA, but also by other

molecules present in the egg. Many genes important or

development are transcribed during ormation o the egg,

and the proteins produced rom these genes can infu-

ence zygotic development in important ways, even i the

genes themselves are lost during meiosis.

Importantly, the brie indeterminacy o the zygotic

genome is a problem or dening when a new individual

comes into existence only i a unique diploid genome

is denitional o an individual human being that is,

i the unique genome is both necessary and sucient

or a human being to be present. Although this kind o

DNA essentialism seems highly intuitive to many, it is

prooundly inadequate as a basis or determining whether

a unique individual exists. I a unique human genome

denes a human being, then identical twins are a single

person, not two individuals. Similarly, i my unique DNA is

denitional o me, then my body is an aggregate, and ev-

ery cell in my body is a unique human beinga clone o

me. Finally, cells removed rom my body and maintained

in the laboratory are also in possession o my unique

genome and must also be clones o me, deserving o all

rights and respect conerred upon me as a human being.

Based on these ew examples, it is clear that possession

o a unique human genome is neither necessary (as in the

case o identical twins) nor sucient (as in the case o

isolated cells) to dene a unique human being.

15 Benjamin Loppin et al., The Histone H3.3 Chaperone

HIRA is Essential or Chromatin Assembly in the Male

Pronucleus, Nature437, no. 7063 (October 27, 2005):

1386-90; Godried W. van der Heijden et al., Asym-

metry in Histone H3 Variants and Lysine Methylation

Between Paternal and Maternal Chromatin o the Early

Mouse Zygote, Mechanisms of Development122, no. 9

(September 2005): 1008-22; Godried W. van der Heijden

et al., Sperm-Derived Histones Contribute to Zygotic

Chromatin in Humans, BMC Developmental Biology31,

no. 8 (March 2008): 34.

16 Helen Fulka et. al, DNA Methylation Pattern in HumanZygotes and Developing Embryos, Reproduction128, no.

6 (December 2004): 703-8; Fatima Santos et al.,

Dynamic Reprogramming o DNA Methylation in the

Early Mouse Embryo, Developmental Biology241,

no. 1 (January 2002): 172-82; Nathalie Beaujean et

al., Non-Conservation o Mammalian Preimplantation

Methylation Dynamics, Current Biology14, no. 7 (April

2004): R266-7.


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17 Gemma Capmany et al., The Timing o Pronuclear

Formation, DNA Synthesis and Cleavage in the Human

1-cell Embryo, Molecular Human Reproduction2, no.

(May 1996): 299-306.

18 Pierre Comizzoli et al.,Onset o the First S-phase i

Determined by a Paternal Eect During the G1-phase i

Bovine Zygotes, Biology of Reproduction62, no. 6 (Ju

2000): 1677-84; J. Schabronath and K. Grtner, Pater

Infuence on Timing o Pronuclear DNA Synthesis in

Naturally Ovulated and Fertilized Mouse Eggs, Biology

Reproduction38, no. 4 (May 1988): 744-9.

19 See ootnote 9.

20 Toshio Hamatani et al., Dynamics o Global Gene

Expression Changes During Mouse Preimplantation De

velopment, Developmental Cell6, no. 1 (January 2004

117-31; Toshio Hamatani et al., Global Gene Expressio

Proling o Preimplantation Embryos Human Cell19,no. 3 (August 2006): 98-117. See also Diane M.Worrad

Prahlad T. Ram, and Richard M. Schultz, Regulation o

Gene Expression in the Mouse Oocyte and Early Preim-

plantation Embryo: Developmental Changes in Sp1 and

TATA Box-binding Protein, TBP,Development120, no.

(August 1994): 2347-57, and reerences therein.

21 Fugaku Aoki, Diane M. Worrad, and Richard M.

Schultz, Regulation o Transcriptional Activity During

the First and Second Cell Cycles in the Preimplanta-

tion Mouse Embryo, Developmental Biology181, no.

2 (January 1997): 296-307; Marie Wiekowski, Miriam

Miranda, and Melvin L. DePamphilis, Requirements

or Promoter Activity in Mouse Oocytes and Embryos

Distinguish Paternal Pronuclei rom Maternal and Zygo

Nuclei, Developmental Biology159, no. 1 (September

1993): 366-78; Pierre G. Adenot et al., Dierential H4

Acetylation o Paternal and Maternal Chromatin Preced

DNA Replication and Dierential Transcriptional Activity

in Pronuclei o 1-cell Mouse Embryos Development1

no. 22 (November 1997): 4615-25.

maternally derived DNA.21 Tis dierential transcription again indicates that thetwo halves o the genome interact prior to syngamy, even though they are located inphysically separate compartments within the zygote.

Gradually, the two pronuclei move towards the center o the cell, in preparation orthe rst cell division (i.e., mitosis) o the zygote (Figure 1E). Immediately prior tocell division, syngamy occurs. Although syngamy is oten characterized as the unit-ing o the two halves o the genome to generate a single diploid nucleus, in act,syngamy is little more than the breakdown o the nuclear membranes that separatethe two pronuclei. No single nucleus is ormed at this point since there is no nu-cleus at all. Te maternally and paternally derived chromosomes are merely presentin the same general region o the cytoplasm. Tis physical co-localization is requiredor accurate segregation o the chromosomes during cell division, so that both cells othe two-cell embryo inherit identical DNA. Following nuclear membrane breakdown(i.e., syngamy), the rst mitotic division o the zygote takes place, thus completingthe rst cell cycle and generating the two-cell embryo (Figure 1F).

From this time orward, although many complex interactions will occur betweencells as the mature body is gradually produced, on the intracellular level DNA repli-cation and cell division will proceed in more or less the standard way that is com-mon to all body cells. Tus, the events o the rst cell cycle, which modiy the DNAcontributed by sperm and egg to enable the participation o this DNA in embryonicdevelopment, are unique to the zygote and to the rst cell cycle (i.e., the rst dayollowing sperm-egg usion).

Based on this actual description o the events ollowing sperm-egg binding, we cancondently conclude that a new cell, the zygote, comes into existence at the mo-ment o sperm-egg usion, an event that occurs in less than a second. At the pointo usion, sperm and egg are physically unitedi.e., they cease to exist as gametes,and they orm a new entity that is materially distinct rom either sperm or egg. Tebehavior o this new cell also diers radically rom that o either sperm or egg: thedevelopmental pathway entered into by the zygote is distinct rom both gametes.Tus, sperm-egg usion is indeed a scientically well dened instant in which thezygote (a new cell with unique genetic composition, molecular composition, andbehavior) is ormed.

!

Nuclear

membranes

breakdown

Fig 1E Syngamy

!Fig 1F Two-Cell Embryo

IS THE zYgOTE MERELY A NEW HUMAN CELL OR

IS IT A NEW HUMAN INdIVIdUAL?

Te events immediately ollowing sperm-egg usion provide incontrovertible evi-dence that a new human cell, the zygote, is produced by this event. Yet, these obser-vations do not address whether the lie o a new human individual has commenced.Is the zygote merely a new kind o cell, or is it a newhuman beinga distinct,individual human organism?


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Te question o precisely when a new human organism comes into existence wasnta matter o practical importance until the advent oin vitro ertilization and hu-man embryo research. Consequently, scientists, philosophers, and bioethicists havenot considered this question in great detail until recently; and appealing to experts(embryologists and ethicists alike) yields a plethora o opinions, oten with very littleactual evidence to support them. o address this question based on the scienticevidence, it is important to distinguish clearly between human cells and humanorganisms.

An organism is dened as (1) a complex structure o interdependent and subordi-nate elements whose relations and properties are largely determined by their unctionin the whole and (2) an individual constituted to carry on the activities o lie bymeans o organs separate in unction but mutually dependent: a living being.22 Tisdenition stresses the interaction o parts in the context o a coordinated whole asthe distinguishing eature o an organism.

Based on this denition, it has been proposed that human beings (including embry-onic human beings) can be reliably distinguished rom human cells using the same

kinds o criteria scientists employ to distinguish dierent cell types: by examiningtheir composition and their pattern o behavior.23 A human being (i.e., a human or-ganism) is composed o characteristic human parts (cells, proteins, RNA, DNA), yetit is dierent rom a mere collection o cells because it has the characteristic behavioro an organism: it acts in an interdependent and coordinated manner to carry onthe activities o lie. In contrast, collections o human cells are alive and carry on theactivities o cellular lie, yet ail to exhibit coordinated interactions directed towardsany higher level o organization. Collections o cells do not establish the complex,interrelated cellular structures (tissues, organs, and organ systems) that exist in awhole, living human being. Similarly, a human corpse is not a living human organ-ism, despite the presence o living human cells within the corpse, precisely becausethis collection o human cells no longer unctions as an integrated unit.24

Is a human zygote a human organism? For developing humans, the behavior andstructures associated with adult stages o lie are not yet ully maniest (embryosneither look like nor act like mature human beings). However, developing humanbeings are composed o characteristic human parts and they exhibit a human patterno developmental behavior. Te key eature o a human pattern o development is itsorganization towards the production o a mature human body.

Te key eature o a human pattern o development isits organization towards the production o a maturehuman body.

22 http://www.merriam-webster.com/dictionary/organism

(accessed 10/1/2008; denition on le with the author).

The second denition is also given verbatim by the

National Library o Medicine, administered by the National

Institutes o Health (http://www.nlm.nih.gov/medlineplus/

mplusdictionary.html).

23 Maureen L. Condic and Samuel B. Condic, Dening

Organisms by Organization, National Catholic Bioethics

Quarterly5: 331-353.

24 Maureen L. Condic, Lie: Dening the Beginning by

the End, First Things133: 50-54.


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7

From the moment o sperm-egg usion, a human zygote acts as a complete whole,with all the parts o the zygote interacting in an orchestrated ashion to generate thestructures and relationships required or the zygote to continue developing towardsits mature state. Everything the sperm and egg do prior to their usion is uniquelyordered towards promoting the binding o these two cells. Everything the zygote doesrom the point o sperm-egg usion onward is uniquely ordered to preventurtherbinding o sperm and to promote the preservation and development o the zygoteitsel. Te zygote acts immediately and decisively to initiate a program o developmentthat will, i uninterrupted by accident, disease, or external intervention, proceed seam-lessly through ormation o the denitive body, birth, childhood, adolescence, matu-rity, and aging, ending with death. Tis coordinated behavior is the very hallmark oan organism.

Mere human cells, in contrast, are composed o human DNA and other humanmolecules, but they show no global organization beyond that intrinsic to cells inisolation. A human skin cell removed rom a mature body and maintained in thelaboratory will continue to live and will divide many times to produce a large masso cells, but it will not re-establish the whole organism rom which it was removed; itwill not regenerate an entire human body in culture. Although embryogenesis beginswith a single-cell zygote, the complex, integrated process o embryogenesis is theactivity o an organism, not the activity o a cell.

Based on a scientic description o ertilization, usion o sperm and egg in themoment o conception generates a new human cell, the zygote, with composition

and behavior distinct rom that o either gamete. Moreover, this cell is not merely aunique human cell, but a cell with all the properties o a ully complete (albeit imma-ture) human organism; it is an individual constituted to carry on the activities o lieby means o organs separate in unction but mutually dependent: a living being.25

25 See ootnote 22.

WHY ISNT SYNgAMY THE BEgINNINg

OF A NEW HUMAN LIFE?

Syngamy, the breakdown o nuclear membranes in preparation or cell division, iscommonly held to be the point at which the zygote is ormed and lie begins. Tisdenition does not deny that a new cell with unique composition and behavior isormed at sperm-egg usion (a pre-zygote, perhaps), but it ails to speciy the nature

o this cell. Te reasons or identiying syngamy as the beginning o lie are two-old.First, syngamy is the last event associated with the rst cell cycle and thus representsthe completion o this unique period o development. Ater this point, many inter-esting and complex interactions occur, but the cells o the embryo behave in mannersthat are also seen in other, more mature body cells. Tus, according to some, synga-my marks the end o the process o ertilization and the onset o a developmentaltrajectory driven by the zygote itsel. Second, many believe that syngamy represents


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8

the usion o the maternally and paternally derived hal-genomes, and the genera-tion o the mature, diploid genome that is unique to the new individual. Both othese assertions are scientically inaccurate.

26 A good analogy or the communication between the

maternally and paternally derived halves o the genome

is the communication o two Internet-linked computers

with dierent data sets that are executing a common

program. The computers will transmit inormation and

mutually modiy each others unction via electronic

signals that are carried by data cables or telephone lines.

The mechanism o this indirect communication will not besubstantially dierent or computers separated by a ew

eet than or those separated by a ew thousand miles;

computers located in the same room are not somehow

more united by virtue o their physical proxim-

ity than are computers located in dierent countries.

Similarly, DNA communicates indirectly and remotely

via DNA-binding proteins, and this communication is

not dependent on physical proximity. So long as the two

halves o the genome are contained within a single cell

(i.e., there is a common mechanism or communication

between dierent elements o the genome), interaction

between maternally and paternally derived DNA happens

indirectly through transcription and translation o DNA

binding proteins, mechanisms that do not require the DNA

to be united within a single nuclear membrane.

27 Wolgang Mayer et al., Spatial Separation o Parental

Genomes in Preimplantation Mouse Embryos, Journal

of Cell Biology148, no. 4 (February 21, 2000): 629-34;Seungeun Yeo et al., Methylation Changes o Lysine 9 o

Histone H3 During Preimplantation Mouse Development,

Molecules and Cells20, no. 3 (December 2005): 423-8;

Fatima Santos et al., Dynamic Reprogramming o DNA

Methylation in the Early Mouse Embryo, Developmental

Biology241, no. 1 (January 2002): 172-82; Jacqueline

Bomar et al., Dierential Regulation o Maternal and

Paternal Chromosome Condensation in Mitotic Zygotes,

Journal of Cell Science115, no. 14 (July 15, 2002):

2931-40.

Compared with the changes in both material composition and developmentaltrajectory that occur at the usion o sperm and egg, syngamy is undamentallyan arbitrary denition or the beginning o lie. From a biological perspective, thebreakdown o nuclear membranes at syngamy is a relatively mundane event alongan already progressingdevelopmental trajectory. Te material composition o the celldoes not change rom the instant prior to syngamy to the instant ater it takes place.Tere is no substantive change in the behavior o the cell at syngamy; all the prepara-tions or cell division (DNA replication, assembly o the mitotic spindle, chromatincondensation) are already underway as the pronuclei move together. Indeed, nuclearmembrane breakdown is not a unique, zygote-orming event, but rather it ispart o every round o cell division that occurs through lie. Te zygote is the samecelland it continues doing exactly what it was doing (i.e., preparing to undergo

cell division) both beore and ater the pronuclei come into physical proximity. Tedevelopmental program observed during the rst cell cycle (including the breakdowno nuclear membranes at syngamy) is clearly initiated by the usion o the sperm andegg, and it progresses seamlessly rom that instant orward.

Te assertion that the mature, diploid genome orms at syngamy is also scienticallyuntenable. Te denitive diploid genome is ormed at the completion o meiosis.As detailed above, although syngamy appears to result in the usion o the twopronuclei, the maternally and paternally derived DNA interact extensively priorto syngamy. Te physical proximity o the two halves o the genome achieved aternuclear membrane breakdown is biologically irrelevant to the ongoing interactiono the DNA contained within the genome.26 Moreover, the mingling o the DNAthat occurs at syngamy is in some ways quite supercial. Tere is good evidence that

ull mingling o the maternal and paternal DNA strands is not completed during therst cell cycle, but rather that chromatin derived rom each parent occupies distinctdomains within the nucleus until at least the our-cell stage.27 Tus, syngamy doesnot ully establish the normal state o a diploid nucleus (as is seen in mature somaticcells, with random mixing o DNA strands derived rom both parents), urther com-promising syngamy as a denition o when the lie o a new individual begins.

Compared with the changes in both material composition anddevelopmental trajectory that occur at the usion o sperm andegg, syngamy is undamentally an arbitrary defnition or thebeginning o lie.


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9

Te essential problem with the view that lie begins at syngamy is the notion thata cell can change rom one type (a pre-zygote that exists ollowing sperm-egg u-sion but prior to syngamy) into another type (the zygote that exists ater syngamy)without any actual change in the material state or behavioral trajectory o the cell.Tis argument is simply not consistent with the scientic method. o assert that liebegins at syngamy is to propose some orm o mysticism: although a zygote cannotbe distinguished in any signicant manner rom the pre-zygote that precedes it, thecell is now a zygote simply because one asserts that it is.

Regardless o how intuitively plausible syngamy may seem as a marker or the onseto a new cell (the zygote), without a demonstrable change in the material and/or thebehavioral state o the cellthat is, without credible scientic evidencethat a newcell type comes into existence at this pointone simply cannot assert that syngamymarks the beginning o a new human cell type, much less a new human being.

WHAT ARE PARTHENOTES, HYdATIdIFORM

MOLES, ANd CLONES?

Dening the beginning o lie as the point at which a new, single-cell organism withunique composition and behavior is ormed raises concerns about a number o enti-ties that appear to be closely related to embryos. In particular, parthenotes, hydatidi-orm moles, and human clones raise issues that need to be careully considered.

28 Christoph Vorburger, Geographic Parthenogenesis

Recurrent Patterns Down Under, Current Biology16,

no. 16 (August 22, 2006): R641-3; Robert G. Edwards,

The Signicance o Parthenogenetic Virgin Mothers in

Bonnethead Sharks and Mice, Reproductive BioMedic

Online15, no. 1 (July 2007): 12-5; T. V. Groot, E. Bruins

and J. A. Breeuwer, Molecular Genetic Evidence or

Parthenogenesis in the Burmese Python, Python Molur

Bivittatus, Heredity90, no. 2 (February 2003): 130-5;

G. Cassar, T. M. John, and R. J. Etches, Observations

on Ploidy o Cells and on Reproductive Perormance in

Parthenogenetic Turkeys, Poultry Science77, no. 10

(October 1998): 1457-62.

29 See discussion o human parthenogenesis in Mahe

dra Rao and Maureen L. Condic, Alternative Sources

Pluripotent Stem Cells: Scientic Solutions to an Ethica

Dilemma, Stem Cells and Development17, no. 1: 1-1

In many animal species, mature egg cells can be induced to divide in the absence osperm by external administration o an electrical pulse or a chemical stimulus thatmimics some aspects o ertilization. Depending on the species, such parthenotes willprogress through a sequence o developmental events that are quite similar to the devel-opment o a zygote. Indeed, in some species o animals, parthenotes occur spontane-ously and can mature to ully ormed adults.28 However, or most species, including allmammals thus ar studied, parthenotes do not develop normally or survive to birth.

Are parthenotes organisms? In the case o mammals, although parthenotes are similarto zygotes in certain respects, there are signicant dierences. Parthenotes containonly maternal chromosomes and, thereore, have a composition that is distinct roma zygote. Importantly, there is no strong evidence that human parthenotes exhibitglobally coordinated activity o parts to generate an integrated pattern o devel-opment.29 Te act that certain aspects o early zygotic behavior can be mimicked

Cloning presents a challenge to the proposed defnitiono when lie begins because cloning does not involve theunion o sperm and egg.


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articially in the laboratory by delivering electrical or chemical stimulation to anoocyte in no way compromises the account o when lie begins during the interactiono sperm and egg. An electrically stimulated egg is dierent in material compositionrom a bona de zygote, and (on a molecular level) its behavior shows it to be quitedistinct rom a zygote.30

A parallel, yet opposite case is presented by complete hydatidiorm moles, a typeo tumor that arises as a consequence o abnormal ertilization. Most commonly,hydatidiorm moles orm when a normal sperm ertilizes an oocyte that has abnor-mally lost its own genetic material. Tis event results in a tumor-orming cell withonly paternally derived chromosomes. Hydatidiorm moles grow quite rapidly andin some ways mimic a normal pregnancy (indeed, they are oten reerred to as amolar pregnancy). However, because hydatidiorm moles contain only paternallyderived chromosomes, they are distinguishable rom zygotes based on their molecularcomposition. Moreover, hydatidiorm moles behave quite dierently rom embryos:they grow as a chaotic mass o disorganized cells and tissues, all o which are unrelatedto each other or to anything resembling a whole. Despite the act that hydatidiormmoles are generated rom human gametes, they do not exhibit an embryonic patterno organization or molecular composition; they are a collection o human cells, butnot a human organism.

Finally, cloning, or somatic cell nuclear transer (SCN), presents a challenge to theproposed denition o when lie begins because cloning does not involve the uniono sperm and egg. In SCN, the nucleus o an egg is removed and a mature body

(somatic) cell is then used to the empty egg, generating a hybrid cell that contains thegenetic inormation o the body cell. In rare cases (usually less than one in a hundredtransers) the body cell nucleus is reprogrammed by the egg cytoplasm to a state that iscapable o supporting a relatively normal pattern o embryonic development. Althoughhuman cloning has only recently been reported,31 it is likely that improvements in thecloning technique will enable human clones to be reliably generated through SCN.

Does generation o a cloned human embryo or live human baby by SCN compro-mise the denition o when a lie begins? No. Upon transer o a somatic nucleusto an empty egg cell, a new cell is generated that has a material composition and adevelopmental trajectory dierent rom those o either o the two cells that producedit. In the rare cases where this hybrid cell goes on to produce a normal pattern odevelopment, its behavior demonstrates that it is an organism.32 Te production o

human embryos via cloning indicates that although gametes are naturally disposedto generate a new organism upon usion, embryos can also be generated under other,highly articial circumstances. Cloning simply indicates that there is more than oneway to make a zygote; it does not alter the analysis o natural ertilization or compro-mise our ability to determine precisely when ertilization results in an organism thatis both materially and behaviorally distinct rom the gametes that give rise to it.

30 The question o whether human parthenotes can, in

rare cases, exhibit an organismal pattern o development

remains controversial, mostly due to a lack o rigorous

scientic observation. While it is clear that human par-

thenotes do not develop normally, considerable caution

is in order. Although stimulated egg cells do not dier in

molecular composition rom unstimulated eggs, they do

exhibit a radical change in developmental trajectoryor

behavior. Should it be demonstrated that parthenotes

have some degree o coordinated development, it would

raise the concern that they may be severely deective

human organisms.

31 Andrew J. French et al., Development o Human

Cloned Blastocysts Following Somatic Cell Nuclear Trans-

er with Adult Fibroblasts, Stem Cells26, no. 2 (February

2008): 485-93.

32 In cases where the development o the cell produced

by cloning is abnormal or where the clone does not

survive, interpreting the nature o the cell produced by

SCNT is problematic. I such clones exhibit any degree o

normal, organismal coordination, caution would dictate

they should be considered deective organisms.


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dOES A HUMAN BEINg CONTROL

ITS OWN dEVELOPMENT OR IS

IT MANUFACTUREd?

Why has it been so difcult to dene when a human lie begins? Why has the viewthat lie begins at syngamy (or at even later developmental stages) been so compellingor so many scientists and physicians? Tose who advocate syngamy as the beginningo lie appear to nd it intuitively obvious that syngamy completes the unique eventso the rst cell cycle and produces ull union o the gametes; until syngamy occurs,the process o ertilization is still underway. Tose who advocate an even later pointor the onset o lie do so on the basis o a similar argument: the embryo has not yetully ormed until specic structures or processes are in place; until these deningevents occur, the process o ertilization (or o embryo ormation) is still underway.Clearly, i ertilization is seen as a process rather than as an event, then prior to thecompletion o this process the zygote is not yet ully present. Based on this view,the cell that results rom the usion o sperm and egg is not a new individual but,as expressed recently by a colleague, merely a unique human cell in the process obecoming a new human, but not there yet. 33

Tis way o thinking about human development is compelling to many because it issimilar to our thinking about the much more amiliar process o manuacturing. Acar is not a car until it rolls o the assembly lineuntil then it is a bunch o parts inthe process o becoming a car, but not there yet. Similarly, a cake is not a cake untilit comes out o the ovenuntil then it is a variously gooey mass o our, sugar, eggs,

and butter that is gradually becoming a cake.

33 Micheline Mathews-Roth, M.D., Harvard University

(personal communication).

34 Identical twins demonstrate that totipotency may b

preserved in all the cells o a human embryo, up to the

two-cell stage, or even later (identical quintuplets are e

tremely rare, but have been observed). The phenomen

o twinning does not alter the importance o the zygote

producing its own development based on an internal

developmental program. Twinning merely indicates tha

when cells o the early embryo are separated, they reta

this internal developmental potency and are able to

regenerate the missing cellular components to produce

complete pattern o human development.

However, a proound dierence exists between manuacturing and embryonic de-velopment. Te dierence is who (or what) is doing the producing. Te embryo isnot something that is being passively built by the process o development, with some

unspecied, external builder controlling the assembly o embryonic components.Rather, the embryo is manuacturing itsel. Te organized pattern o development doesntproduce the embryo; it is produced bythe embryo as a consequence o the zygotesinternal, sel-organizing power. Indeed, this totipotency, or the power o the zygoteboth to generate all the cells o the body and simultaneously to organize those cells intocoherent, interacting bodily structures, is the dening eature o the embryo. 34

Te embryo is not something that is being passively builtby the process o development, with some unspecifed,external builder controlling the assembly o embryoniccomponents. Rather, the embryo is manuacturing itsel.


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An additional problem with comparing embryogenesis to manuacturing is that, un-like the building o an automobile, there is no actual endpoint to the building o ahuman being. Human development is an ongoingprocess that begins with the zygoteand continues seamlessly through embryogenesis, etogenesis, birth, maturation, andaging, ending only in death. I the zygote is a manuactured product o an ongo-ing developmental process, at what point along this continuum does a human beingactually exist? Why is a cell that has undergone syngamy a human zygote and notmerely a unique human cell in the process o becoming a new human, but not thereyet? Indeed, why consider the entity present at the end o embryogenesis or at birtha human being, and not merely a unique collection o human cells in the process obecoming a new human, but not there yet? Once a concession has been made to theconcept o manuacture and to an arbitrary point at which development has pro-ceeded ar enough along the assembly line to generate a human being, the precisepositioning o this point becomes purely a matter o preerence, convenience, andthe power to enorce ones view.

In contrast, i the embryo comes into existence at sperm-egg usion, a human organ-ism is ully present rom the beginning, controlling and directing all o the develop-mental events that occur throughout lie. Tis view o the embryo is objective, basedon the universally accepted scientic method o distinguishing dierent cell typesrom each other, and it is consistent with the actual evidence. It is entirely indepen-dent o any specic ethical, moral, political, or religious view o human lie or ohuman embryos. Indeed, this denition does not directly address the central ethicalquestions surrounding the embryo: What valueought society to place on human lie

at the earliest stages o development? Does the human embryo possess the same rightto lie as do human beings at later developmental stages? A neutral examination othe actual evidence merely establishes the onset o a new human lie at a scienti-cally well dened moment o conception, a conclusion that unequivocally indicatesthat human embryos rom the zygote stage orward are indeed living individuals othe human specieshuman beings.


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Dr. Condic is an Associate Proessor o Neurobiology and Anatomy at the Universityo Utah School o Medicine, with an adjunct appointment in the Department o Pe-diatrics. She received her undergraduate degree rom the University o Chicago, andher doctorate rom the University o Caliornia at Berkeley. Since her appointmentat the University o Utah in 1997, Dr. Condics primary research ocus has beenthe development and regeneration o the nervous system. In 1999, she was awardedthe Basil OConnor Young Investigator Award or her studies o peripheral nervoussystem development. In 2002, she was named a McKnight Neuroscience o BrainDisorders Investigator in recognition o her research in the eld o adult spinal cordregeneration. In addition to her scientic research, Dr. Condic participates in bothgraduate and medical teaching. She is director o the University o Utah School oMedicine course in Human Embryology. She has published and presented seminarsnationally on issues concerning science policy and the ethics o biological research.Dr. Condic currently resides in Salt Lake City with her husband and our children.

Maureen L. Condic, Ph.D.Department o Neurobiology and Anatomy, University o Utah School o MedicineSalt Lake City, U [email protected]

AUTHOR


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centromere: the point or region on a chromosome to which the spindle attachesduring mitosis and meiosisalso called kinetochore.

chromatin: a complex o a nucleic acid with basic proteins (as histone) in eukaryoticcells that is usually dispersed in the interphase nucleus and condensed into chromo-somes in mitosis and meiosis.

chromosome: any o the usually linear bodies o the cell nucleus o eukaryotic or-ganisms that take up basophilic stains and contain most or all o the genes o the or-ganism; a condensed orm o chromatin ound prior to cell division. When chromosomeshave replicated, but are still attached at the centromere, they are called sister chromatids.

demethylation: the process o removing a methyl group rom a chemical compound.Methyl groups bound to DNA generally inhibit DNA unction.

diploid: having the basic (haploid) chromosome number doubled. Diploid is thenormal state or somatic (i.e., body) cells.

DNA: any o various nucleic acids that are usually the molecular basis o heredity,that are constructed o a double helix held together by hydrogen bonds betweenpurine and pyrimidine bases, which project inward rom two chains containing alter-nate links o deoxyribose and phosphate, and that in eukaryotes are localized chieyin cell nuclei also called deoxyribonucleic acid.

embryo: an animal in the early stages o growth and dierentiation that is charac-terized by cleavage, the laying down o undamental tissues, and the ormation o

primitive organs and organ systems; especially the developing human individual romthe time oertilization to the end o the eighth week ater conception (cleavage com-mences immediately ater ertilization at the two cell stage).

eukaryote: any o a domain (Eukarya) or a higher taxonomic group (Eukaryota)above the kingdom that includes organisms composed o one or more cells contain-ing visibly evident nuclei and organelles.

fertilization: the process o union o two gametes whereby the somatic chromosomenumber is restored and the development o a new individual is initiated.

gamete: a mature male or emale germ cell (sperm or egg) usually possessing a hap-loid chromosome set and capable o initiating ormation o a new diploid individualby usion with a gamete o the opposite sex also called sex cell.

gene: a specic sequence o nucleotides in DNA that is located usually on a chromo-some and that is the unctional unit o inheritance controlling the transmission andexpression o one or more traits by speciying the structure o a particular polypep-tide and especially a protein or controlling the unction o other genetic material also called determinant, determiner, actor.

gLOSSARY*

* All denitions are taken rom the NIH-administered

medical dictionary, (accessed 10/1/08; denitions on

le with author; http://www.nlm.nih.gov/medlineplus/

mplusdictionary.html) with minor modications or clarity,

as indicated by italics.


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genome: one haploid set o chromosomes with the genes they contain.

haploid: having the gametic number o chromosomes or hal the number character-istic o somatic cells.

histone: any o various simple water-soluble proteins that are rich in the basic aminoacids lysine and arginine and are complexed with DNA.

hydatidiform mole: a mass in the uterus that consists o enlarged edematous degen-erated chorionic villi, growing in clusters resembling grapes, that typically developsollowing ertilization o an enucleate egg, and that may or may not contain etaltissue.

meiosis: the cellular process that results in the number o chromosomes in gamete-producing cells being reduced to one hal and that involves a reduction division inwhich one o each pair o homologous chromosomes passes to each daughter cell anda mitotic division.

mitosis: a process that takes place in the nucleus o a dividing cell, involves typicallya series o steps consisting o prophase, metaphase, anaphase, and telophase, andresults in the ormation o two new nuclei each having the same number o chromo-somes as the parent nucleus.

nucleus: a cellular organelle o eukaryotes that is essential to cell unctions (as repro-duction and protein synthesis), is composed o nuclear sap and a nucleoprotein-richnetwork rom which chromosomes and nucleoli arise, and is enclosed in a denite

membrane.organism: an individual constituted to carry on the activities o lie by means oorgans separate in unction but mutually dependent: a living being.

ovum (oocyte, egg): a emale gameteespecially a mature egg that has undergonereduction, is ready or ertilization, and takes the orm o a relatively large inactivegamete providing a comparatively great amount o reserve material and contributingmost o the cytoplasm o the zygote.

parthenote:an individual ormed bydevelopment o an unertilized, usually emale,gamete that occurs especially among lower plants and invertebrate animals.

pronucleus: the haploid nucleus o a male or emale gamete (as an egg or sperm) up

to the time o usion with that o another gamete in ertilization.protamine: any o various strongly basic proteins o relatively low molecular weightthat are rich in arginine and are ound, associated especially with DNA, in place ohistone in the sperm o various animals.


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RNA: any o various nucleic acids that contain ribose and uracil as structural compo-nents and are associated with the control o cellular chemical activitiescalled alsoribonucleic acid. Messenger RNA is an RNA produced by transcription that carriesthe code or a particular protein rom the nuclear DNA to a ribosome in the cyto-plasm and acts as a template or the ormation o that proteinalso called mRNA.

SCNT/Cloning:Somatic cell nuclear transer (SCN); transplanting nuclei rombody(i.e., somatic) cells to enucleated eggs.

sister chromatid: see chromosome.

sperm (spermatozoa): a sperm cell; a motile male gamete o an animal usually withrounded or elongate head and a long posterior agellum.

syngamy: sexual reproduction by union o gametes. Commonly used to reer to thebreak-down o nuclear membranes o the pronuclei approximately 24 hours ater sperm-egg usion.

transcription: the process o constructing a messenger RNA molecule using a DNAmolecule as a template with resulting transer o genetic inormation to the messen-ger RNA.

translation: the process o orming a protein molecule at a ribosomal site o proteinsynthesis rom inormation contained in messenger RNA.

zona pellucida: the transparent more or less elastic noncellular glycoprotein outerlayer or envelope o a mammalian ovum.

zygote: a cell ormed by the union o two gametes; broadly, the developing individu-al produced rom such a cell.


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17

!Zona

Pellucida

Ovum

Sperm

Maternalnucleus

!

Paternal

nucleus

Zygote

!Polar

body

Paternal

nucleus

!

!

Nuclear

membranes

breakdown

!

A. Sperm-egg fusion: Prior to usion, thematernal nucleus is arrested at meiosis II. Sisterchromatids (one pair illustrated) are non-identical due to genetic recombination duringoogenesis.

B. Zygote formation: Te zygote orms im-mediately upon sperm-egg usion. Factors romthe sperm initiate completion o meiosis II inthe maternally derived nucleus. Within 1-3minutes, changes in cellular calcium initiatethe cortical reaction o the zygote, making thecell reractory to usion with other sperm.

C. Early acts of the zygote: Within 30minutes, meiosis II is complete, establish-ing the nal diploid genome o the zygote.Sperm binding sites in the zona pellucida aredestroyed. Both nuclei undergo decondensa-tion. Paternal DNA is more rapidly and moreextensively demethylated than maternal DNA.

D. Onset of zygotic transcription: DNA rep-lication begins at 8-10 hours, converting both

nuclei to a (2N) state. ranscription commenc-es immediately ollowing DNA replication.Te paternal nucleus suppresses transcriptionin the maternal nucleus.

E. Syngamy: Ater approximately 20-25 hours,the pronuclei move together and their nuclearmembranes break down. Te chromosomesalign and mitosis begins immediately.

F. Two-cell embryo: Cell division generates atwo-cell embryo. ranscription increases anddevelopment beyond this stage depends on zy-

gotic transcription. Evidence suggests that eachcell is biased towards distinct developmentalpaths, and that they interact coordinately toorchestrate subsequent development.

FIgURE 1A.

B.

C.

D.

E.

F.


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18

Anderson, Ryan ., and Maureen L. Condic, Proessor Lee Silvers Vast ScienticConspiracy. First Tings: On the Square. January 14, 2008. http://www.rstth-ings.com/onthesquare/?p=946.

Berg, Tomas. Te Personhood o the Human Embryo. Homiletic and PastoralReview 103, no. 7 (April 2003): 10-19.

Berg, Tomas V., and Maureen L. Condic, Emerging Biotechnologies, the Deense oEmbryonic Human Lie, and Altered Nuclear ranser. Linacre Quarterly(orth-coming).

Condic, Maureen L. Alternative Sources o Pluripotent Stem Cells: Altered Nuclearranser. Cell Prolieration 41, Suppl. 1 (2008): 7-19.

---. Te Beginning o Lie: A Perspective rom Science. DeVos Medical Ethics Colloquy.Grand Rapids: Van Andel Press, 2007.

---. Lie: Dening the Beginning by the End. First Tings133: 50-54.Condic, Maureen L., and Samuel B. Condic. Dening Organisms by Organiza-

tion. National Catholic Bioethics Quarterly5, no. 2: 331-53.Condic, Maureen L., and E. J. Furton. Harvesting Embryonic Stem Cells rom

Deceased Human Embryos.National Catholic Bioethics Quarterly7, no. 3: 507-525.George, Robert P., and Alonso Gomez-Lobo. Te Moral Status o the Human Em-

bryo. Perspectives in Biology and Medicine48, no. 2 (Spring 2005): 201-10.George, Robert P., and Patrick Lee. Te Embryo Question I: Acorns and Embryos.

New Atlantis7 (Fall 2004 Winter 2005): 90-100.George, Robert P., and Christopher ollesen. Embryo: A Deense o Human Lie.

New York: Doubleday, 2008.Hurlbut, William, Robert P. George, and Markus Grompe. Seeking Consensus: A

Clarication and Deense o Altered Nuclear ranser. Hastings Center Report45 (September-October 2006).Lee, Patrick. Abortion and Unborn Human Lie. Washington, DC: Catholic Univer-

sity o America Press, 1996.Lee, Patrick, and Robert P. George. Te First Fourteen Days o Human Lie. New

Atlantis13 (Summer 2006): 61-7.Rao, Mahendra, and Maureen L. Condic. Alternative Sources o Pluripotent Stem

Cells: Scientic Solutions to an Ethical Dilemma. Stem Cells and Development17, no. 1: 1-10.

SELECT BIBLIOgRAPHY


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Te Westchester Institute or Ethics & the Human Person is a research institute conductinginterdisciplinary, natural law analysis o complex, contemporary moral issues as yet unre-solved among Judeo-Christian scholars.

Anchored in the classic perennial and Catholic view o the human person, our moral in-quiries are rst and oremost o a scholarly nature. However, we pursue answers to disputedquestions with an eye toward enriching the quality o contemporary moral discourse andostering sound prudential judgment in cultural and political matters.

We are currently dedicated to the ollowing issues:

Tegenesisofhumanlifeandthemoralstatusofthehumanembryo Tesearchforscienticallyandmorallyfeasiblealternativestoembryo-based

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